Abstract
CVID patients have an increased susceptibility to vaccine-preventable infections. The question on the potential benefits of immunization of CVID patients against SARS-CoV-2 offered the possibility to analyze the defective mechanisms of immune responses to a novel antigen. In CVID, as in immunocompetent subjects, the role of B and T cells is different between infected and vaccinated individuals. Upon vaccination, variable anti-Spike IgG responses have been found in different CVID cohorts. Immunization with two doses of mRNA vaccine did not generate Spike-specific classical memory B cells (MBCs) but atypical memory B cells (ATM) with low binding capacity to Spike protein. Spike-specific T-cells responses were also induced in CVID patients with a variable frequency, differently from specific T cells produced after multiple exposures to viral antigens following influenza virus immunization and infection. The immune response elicited by SARS-CoV-2 infection was enhanced by subsequent immunization underlying the need to immunize convalescent COVID-19 CVID patients after recovery. In particular, immunization after SARS-Cov-2 infection generated Spike-specific classical memory B cells (MBCs) with low binding capacity to Spike protein and Spike-specific antibodies in a high percentage of CVID patients. The search for a strategy to elicit an adequate immune response post-vaccination in CVID patients is necessary. Since reinfection with SARS-CoV-2 has been documented, at present SARS-CoV-2 positive CVID patients might benefit from new preventing strategy based on administration of anti-SARS-CoV-2 monoclonal antibodies.
Highlights
The Committee of Experts on Primary Immunodeficiency of the International Union of Immunological Societies (IUIS) has included vaccination both as a diagnostic tool to assess the specific antibody response to protein and/or polysaccharide antigens and as a means of prevention [1].SARS-CoV-2 Vaccine in common variable immunodeficiency (CVID)The type and severity of the immunodeficiency determines the efficacy of vaccines, with varying levels of impairment, ranging from normal as in immunocompetent individuals, to incomplete or even absent
Immunization of CVID patients against SARS-CoV-2 offered the possibility to analyze how defective mechanisms impact the immune response to a novel antigen
Discrepancy in the results published on antibody responses after SARS-CoV-2 immunization in CVID might be due to the heterogeneity of CVID populations enrolled or to different vaccination protocols
Summary
The Committee of Experts on Primary Immunodeficiency of the International Union of Immunological Societies (IUIS) has included vaccination both as a diagnostic tool to assess the specific antibody response to protein and/or polysaccharide antigens and as a means of prevention [1]. Whereas we expect that after the initial decline, antibody levels will reach a plateau in control subjects reflecting the establishment of the long-lived memory plasma cell pool, this may never happen in CVID and antibodies may rapidly become undetectable For this reason, antibody measurement, month after vaccination, is neither indicated nor useful for the majority of vaccinees, the change in the concentration of Spike specific antibodies may represent an important measure of the ability of CVID patients to prevent SARS-CoV-2 severe disease. None of the CVID patients generated memory B cells specific for the receptor binding domain (RBD) of SARS-CoV-2, indicating the incapability of CVID B-cells to undergo somatic mutation and affinity maturation in the GC indispensable for the production of neutralizing antibodies This impairment, associated to the generation of atypical memory or classical memory B cells with low affinity for the Spike protein is the basis to hypothesize a sub-optimal and transient humoral immune response after vaccination in CVID patients. The upregulation of gene signature associated with type I and type II IFN production was not observed in the immunized subjects, suggesting an adaptive immunity maturation in the absence of IFN signaling
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